Category: Statistics

Arterioscler Thromb Vasc Biol. 2023 Jan 5. doi: 10.1161/ATVBAHA.122.318149. Online ahead of print.

ABSTRACT

BACKGROUND: Observational studies identified elevated blood pressure (BP) as a strong risk factor for thoracic aortic dilation, and BP reduction is the primary medical intervention recommended to prevent progression of aortic aneurysms. However, although BP may impact aortic dilation, aortic size may also impact BP. The causal relationship between BP and thoracic aortic size has not been reliably established.

METHODS: Genome-wide association studies summary statistics were obtained for BP and ascending thoracic aortic diameter (AscAoD). Causal effects of BP on AscAoD were estimated using 2-sample Mendelian randomization using a range of pleiotropy-robust methods.

RESULTS: Genetically predicted increased systolic BP, diastolic BP, and mean arterial pressure all significantly associate with higher AscAoD (systolic BP: β estimate, 0.0041 mm/mm Hg [95% CI, 0.0008-0.0074]; P=0.02, diastolic BP: β estimate, 0.0272 mm/mm Hg [95% CI, 0.0224-0.0320]; P<0.001, and mean arterial pressure: β estimate, 0.0168 mm/mm Hg [95% CI, 0.0130-0.0206]; P<0.001). Genetically predicted pulse pressure, meanwhile, had an inverse association with AscAoD (β estimate, -0.0155 mm/mm Hg [95% CI, -0.0213 to -0.0096]; P<0.001). Multivariable Mendelian randomization analyses showed that genetically predicted increased mean arterial pressure and reduced pulse pressure were independently associated with AscAoD. Bidirectional Mendelian randomization demonstrated that genetically predicted AscAoD was inversely associated with pulse pressure (β estimate, -2.0721 mm Hg/mm [95% CI, -3.1137 to -1.0306]; P<0.001) and systolic BP (β estimate, -1.2878 mm Hg/mm [95% CI, -2.3533 to -0.2224]; P=0.02), while directly associated with diastolic BP (0.8203 mm Hg/mm [95% CI, 0.2735-1.3672]; P=0.004).

CONCLUSIONS: BP likely contributes causally to ascending thoracic aortic dilation. Increased AscAoD likely contributes to lower systolic BP and pulse pressure, but not diastolic BP, consistent with the hemodynamic consequences of a reduced aortic diameter.

PMID:36601961 | DOI:10.1161/ATVBAHA.122.318149

Stroke. 2023 Jan 5. doi: 10.1161/STROKEAHA.122.040638. Online ahead of print.

ABSTRACT

The Stroke Preclinical Assessment Network (SPAN) is a multicenter preclinical trial platform using rodent models of transient focal cerebral ischemia to address translational failure in experimental stroke. In addition to centralized randomization and blinding and large samples, SPAN aimed to introduce heterogeneity to simulate the heterogeneity embodied in clinical trials for robust conclusions. Here, we report the heterogeneity introduced by allowing the 6 SPAN laboratories to vary most of the biological and experimental model variables and the impact of this heterogeneity on middle cerebral artery occlusion (MCAo) performance. We included the modified intention-to-treat population of the control mouse cohort of the first SPAN trial (n=421) and examined the biological and procedural independent variables and their covariance. We then determined their impact on the dependent variables cerebral blood flow drop during MCAo, time to achieve MCAo, and total anesthesia duration using multivariable analyses. We found heterogeneity in biological and procedural independent variables introduced mainly by the site. Consequently, all dependent variables also showed heterogeneity among the sites. Multivariable analyses with the site as a random effect variable revealed filament choice as an independent predictor of cerebral blood flow drop after MCAo. Comorbidity, sex, use of laser Doppler flow to monitor cerebral blood flow, days after trial onset, and maintaining anesthesia throughout the MCAo emerged as independent predictors of time to MCAo. Total anesthesia duration was predicted by most independent variables. We present with high granularity the heterogeneity introduced by the biological and model selections by the testing sites in the first trial of cerebroprotection in rodent transient filament MCAo by SPAN. Rather than trying to homogenize all variables across all sites, we embraced the heterogeneity to better approximate clinical trials. Awareness of the heterogeneity, its sources, and how it impacts the study performance may further improve the study design and statistical modeling for future multicenter preclinical trials.

PMID:36601951 | DOI:10.1161/STROKEAHA.122.040638

J Synchrotron Radiat. 2023 Jan 1;30(Pt 1):217-226. doi: 10.1107/S1600577522010748. Epub 2023 Jan 1.

ABSTRACT

FOCUS (Fast Monte CarlO approach to Coherence of Undulator Sources) is a new GPU-based simulation code to compute the transverse coherence of undulator radiation from ultra-relativistic electrons. The core structure of the code, which is written in the language C++ accelerated with CUDA, combines an analytical description of the emitted electric fields and massively parallel computations on GPUs. The combination is rigorously justified by a statistical description of synchrotron radiation based on a Fourier optics approach. FOCUS is validated by direct comparison with multi-electron Synchrotron Radiation Workshop (SRW) simulations, evidencing a reduction in computation times by up to five orders of magnitude on a consumer laptop. FOCUS is then applied to systematically study the transverse coherence in typical third- and fourth-generation facilities, highlighting peculiar features of undulator sources close to the diffraction limit. FOCUS is aimed at fast evaluation of the transverse coherence of undulator radiation as a function of the electron beam parameters, to support and help prepare more advanced and detailed numerical simulations with traditional codes like SRW.

PMID:36601940 | DOI:10.1107/S1600577522010748

J Synchrotron Radiat. 2023 Jan 1;30(Pt 1):35-50. doi: 10.1107/S1600577522009973. Epub 2023 Jan 1.

ABSTRACT

A promising accelerator light source mechanism called steady-state microbunching (SSMB) is being actively studied. With the combination of strong coherent radiation from microbunching and high repetition rate of a storage ring, high-average-power narrow-band radiation can be anticipated from an SSMB storage ring, with wavelengths ranging from THz to soft X-ray. Such a novel light source could provide new opportunities for accelerator photon science like high-resolution angle-resolved photoemission spectroscopy and industrial applications like extreme ultraviolet (EUV) lithography. In this paper, a theoretical and numerical study of the average and statistical properties of coherent radiation from SSMB are presented. The results show that 1 kW average-power quasi-continuous-wave EUV radiation can be obtained from an SSMB ring provided that an average current of 1 A and a microbunch train with bunch length of 3 nm can be formed at the radiator which is assumed to be an undulator. Together with the narrow-band feature, the EUV photon flux can reach 6 × 10¹⁵ photons s^-1 within a 0.1 meV energy bandwidth, which is three orders of magnitude higher than that in a conventional synchrotron source and is appealing for fundamental condensed matter physics and other research. In this theoretical investigation, we have generalized the definition and derivation of the transverse form factor of an electron beam which can quantify the impact of its transverse size on coherent radiation. In particular, it has been shown that the narrow-band feature of SSMB radiation is strongly correlated with the finite transverse electron beam size. Considering the pointlike nature of electrons and quantum nature of radiation, the coherent radiation fluctuates from microbunch to microbunch, or for a single microbunch from turn to turn. Some important results concerning the statistical properties of SSMB radiation are presented, with a brief discussion on its potential applications, for example the beam diagnostics. The presented work is of value for the development of SSMB to better serve potential synchrotron radiation users. In addition, this also sheds light on understanding the radiation characteristics of free-electron lasers, coherent harmonic generation, etc.

PMID:36601924 | DOI:10.1107/S1600577522009973

Phlebology. 2023 Jan 5:2683555221149597. doi: 10.1177/02683555221149597. Online ahead of print.

ABSTRACT

BACKGROUND: Peripherally inserted central catheter (PICC) is widely used in clinical practice because of its long retention time and easy maintenance. However, PICC-associated venous thromboembolism (VTE) is the most serious complication of PICC. Guidelines recommend exercise therapy to prevent PICC-associated VTE. However, inconsistent findings have been reported across the literature. This study conducted a meta-analysis to further evaluate the effect of exercise therapy on PICC-associated VTE.

METHODS: We searched CNKI, Wanfang database, Chinese Science and Technology Journal Full Text Database, PubMed, Embase, Web of Science and Cochrane Library databases and included all randomized controlled trials (RCTs) of exercise therapy for the prevention of PICC-associated VTE. Two investigators independently screened the literature, extracted information, and evaluated the risk of bias for eligible RCTs. Meta-analysis was conducted by RevMan5.4 software.

RESULTS: Eleven RCTs were included, including 1919 patients. Meta-analysis showed that the incidence of PICC-associated VTE was lower in the exercise therapy group than in the usual care group (RR = 0.30, 95% CI: 0.22-0.41, p < 0.00001).Exercise therapy increased the axillary vein maximum velocity (SMD = 0.93, 95% CI: 0.58-1.28, p < 0.00001) and the axillary vein time-mean flow velocity (SMD = 0.86, 95% CI: 0.53-1.20, p < 0.00001). Subgroup analysis showed statistically significant differences for the incidence of PICC-associated VTE for intervention times<4 weeks (RR = 0.26, 95% CI: 0.17-0.40, p < 0.00001) and intervention times≥4 weeks (RR = 0.35, 95% CI: 0.22-0.54, p < 0.00001). For axillary vein maximum velocity, the difference was statistically significant for both intervention time <4 weeks (SMD = 0.73, 95% CI: 0.55-0.91, p < 0.00001) and intervention time ≥4 weeks (SMD = 1.18, 95% CI: 0.18-2.19, p = 0.02). For axillary vein time-mean flow velocity, the intervention time <4 weeks (SMD = 0.75, 95% CI: 0.46-1.04, p < 0.00001), and the difference was statistically significant; while ≥4 weeks, the difference was not statistically significant (SMD = 1.14, 95% CI: -0.07 to 2.35, p = 0.06).

CONCLUSIONS: Exercise therapy improved venous blood flow velocity and effectively reduced the incidence of PICC-associated VTE. However, RCTs with large samples and high quality are needed to further evaluate the effectiveness of exercise therapy in PICC patients.

PMID:36601900 | DOI:10.1177/02683555221149597

Pol Arch Intern Med. 2023 Jan 4:16395. doi: 10.20452/pamw.16395. Online ahead of print.

ABSTRACT

INTRODUCTION: The fracture risk assessment is essential for the diagnostic process in osteoporosis.

OBJECTIVE: The aim of the study was to develop an algorithm for fracture risk prediction.

PATIENTS AND METHODS: Bone status was investigated in a population-based cohort of postmenopausal women, their mean age being 66.4 (SD=7.8) years. After that all the participants were invited by phone once a year (for 10 consecutive years) to update their history of fractures. At the end of the 10-year observation period the number of the study participants was 640 women, out of whom, 129 women presented the history of 190 osteoporotic fractures, recorded during the study period. Statistical analysis included multistep data preprocessing, feature selection, identification of fracture risk factors, and a final model design. Logistic regression models were fitted and used for evaluation of variables from determined feature sets, including global fit measures, as well as individual parameters, such as the Wald statistic and P-value, the odds ratio, and the confidence interval.

RESULTS: The 10-year any fracture risk depended on the age of the study subjects, the number of recorded fractures after the age of 40 years, femoral neck bone mass values, and the fact of falls in the past year. The equation is as follows: Risk of fracture=1/(1+e^(-(-3.336+0.019*AGE+0.437*NUMBER_OF_PRIOR_FRACTURES-0.258*FN_T_score+0.508*PRIOR_FALLS)). The algorithm is available at www.fracture-risk.pl.

CONCLUSION: A fracture prediction algorithm was developed in a longitudinal study to calculate 10-year fracture risk. The identification of patients at high fracture risk should be followed by a treatment strategy to reduce the number of future fractures.

PMID:36601872 | DOI:10.20452/pamw.16395

Cancer Invest. 2023 Jan 5:1-8. doi: 10.1080/07357907.2022.2162072. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the diagnostic mismatch (discrepancy) of pathology reports in consulted specimens referred for second opinion.

MATERIALS AND METHODS: This cross-sectional study was conducted at a major cancer center, Omid Hospital. In this study, 350 primary pathology reports and 350 reviewed pathology reports were extracted from the archives of Omid Hospital from 2011 to 2020 and assessed in terms of the extent of discrepancy, by two pathologists and one oncologist. The required data for each sample were entered into a checklist and then statistically analyzed. Cases with the same diagnosis on both reports were assigned to the matched group and the rest were assigned to the minor or major mismatch (discrepancy) group. Minor mismatches included changes in diagnosis that did not lead to changes in treatment (may lead to changes in prognosis or provide additional information to the oncologist) and major mismatches included changes in diagnosis leading to changes in treatment or remedies.

RESULTS: Two hundred seven cases (59.1%) out of three hundred fifty cases had concordant results between the diagnosis of the first pathologist and the reviewing pathologist. In one hundred forty-three cases (40.9%) mismatch (discrepancy) was observed, including eighty- two cases (23.4%) with minor mismatches (discrepancy) and sixty-one cases (17.4%) with major mismatches (discrepancy). In the major mismatch group, fifteen cases (4.3%) changed from malignant to benign, eighteen cases (5.1%) changed from benign to malignant, two cases (0.6%) changed from one stage to another stage of Disease and twenty-six cases (7.4%) had changes in the type of malignancy. In this study, it was found that there was no significant relationship between anatomical areas of sampling and diagnostic mismatch (p = 0.254). The study also found that the rate of diagnostic mismatch in specimens obtained by resection or excisional biopsy was greater than that of small biopsies (eighty cases (22.8%) and sixty-two cases (17.7%, respectively)). There was no significant relationship in this regard (p = 0.077).

CONCLUSION: Compared to most similar studies, the present study reported the highest discrepancy between the diagnosis of the first pathologist and the reviewing pathologist (40.9%).

PMID:36601856 | DOI:10.1080/07357907.2022.2162072

Emerg Nurse. 2023 Jan 5. doi: 10.7748/en.2023.e2127. Online ahead of print.

ABSTRACT

Emergency triage is a short-duration, high-volume process so small reductions in the time taken to triage one patient can have large repercussions on the total amount of triage time. At the emergency department of a large inner-city hospital, an efficiency and quality improvement project was undertaken to reduce the time taken to safely triage patients and optimise the use of triage nurses’ time. The project involved removing processes that did not contribute to the primary aim of triage, supporting individual triage nurses to improve their performance where needed, and optimising the triage process. A 44% reduction in mean triage episode time was seen, equating to 18,000 minutes of triage nurses’ time saved every month. This near doubling of triage capacity was associated with an improvement in triage accuracy. The article describes the project, which used lean management principles and statistical process control methods, and discusses its implications for emergency triage.

PMID:36601815 | DOI:10.7748/en.2023.e2127

Acta Crystallogr D Struct Biol. 2023 Jan 1;79(Pt 1):50-65. doi: 10.1107/S2059798322011871. Epub 2023 Jan 1.

ABSTRACT

It is investigated whether molecular-dynamics (MD) simulations can be used to enhance macromolecular crystallography (MX) studies. Historically, protein crystal structures have been described using a single set of atomic coordinates. Because conformational variation is important for protein function, researchers now often build models that contain multiple structures. Methods for building such models can fail, however, in regions where the crystallographic density is difficult to interpret, for example at the protein-solvent interface. To address this limitation, a set of MD-MX methods that combine MD simulations of protein crystals with conventional modeling and refinement tools have been developed. In an application to a cyclic adenosine monophosphate-dependent protein kinase at room temperature, the procedure improved the interpretation of ambiguous density, yielding an alternative water model and a revised protein model including multiple conformations. The revised model provides mechanistic insights into the catalytic and regulatory interactions of the enzyme. The same methods may be used in other MX studies to seek mechanistic insights.

PMID:36601807 | DOI:10.1107/S2059798322011871

Acta Crystallogr D Struct Biol. 2023 Jan 1;79(Pt 1):31-39. doi: 10.1107/S2059798322011858. Epub 2023 Jan 1.

ABSTRACT

Proteins often assemble into functional complexes, the structures of which are more difficult to obtain than those of the individual protein molecules. Given the structures of the subunits, it is possible to predict plausible complex models via computational methods such as molecular docking. Assessing the quality of the predicted models is crucial to obtain correct complex structures. Here, an energy-scoring function was developed based on the interfacial residues of structures in the Protein Data Bank. The statistically derived energy function (Nepre) imitates the neighborhood preferences of amino acids, including the types and relative positions of neighboring residues. Based on the preference statistics, a program iNepre was implemented and its performance was evaluated with several benchmarking decoy data sets. The results show that iNepre scores are powerful in model ranking to select the best protein complex structures.

PMID:36601805 | DOI:10.1107/S2059798322011858